Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure

Abstract Aims Associations between growth differentiation factor‐15 (GDF‐15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the ‘Functiona...

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Main Authors: Abhinav Sharma, Stephen Greene, Muthiah Vaduganathan, Marat Fudim, Andrew P. Ambrosy, Jie‐Lena Sun, Steven E. McNulty, Adrian F. Hernandez, Barry A. Borlaug, Eric J. Velazquez, Robert J. Mentz, Adam D. DeVore, Brooke Alhanti, Kenneth Margulies, G. Michael Felker
Format: Article
Language:English
Published: Wiley 2021-08-01
Series:ESC Heart Failure
Subjects:
Online Access:https://doi.org/10.1002/ehf2.13348
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author Abhinav Sharma
Stephen Greene
Muthiah Vaduganathan
Marat Fudim
Andrew P. Ambrosy
Jie‐Lena Sun
Steven E. McNulty
Adrian F. Hernandez
Barry A. Borlaug
Eric J. Velazquez
Robert J. Mentz
Adam D. DeVore
Brooke Alhanti
Kenneth Margulies
G. Michael Felker
author_facet Abhinav Sharma
Stephen Greene
Muthiah Vaduganathan
Marat Fudim
Andrew P. Ambrosy
Jie‐Lena Sun
Steven E. McNulty
Adrian F. Hernandez
Barry A. Borlaug
Eric J. Velazquez
Robert J. Mentz
Adam D. DeVore
Brooke Alhanti
Kenneth Margulies
G. Michael Felker
author_sort Abhinav Sharma
collection DOAJ
description Abstract Aims Associations between growth differentiation factor‐15 (GDF‐15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the ‘Functional Impact of GLP‐1 for Heart Failure Treatment’ (FIGHT) study to address these knowledge gaps. Methods and results FIGHT was a randomized clinical trial testing the effect of liraglutide (vs. placebo) among 300 participants with HFrEF and a recent HHF. Multivariable regression models evaluated associations between baseline GDF‐15 and change in GDF‐15 (per 1000 pg/mL increase from baseline to 30 days) with clinical outcomes (at 180 days) and declines in exercise capacity (6 min walk distance ≥ 45 m). At baseline (n = 249), median GDF‐15 value was 3221 pg/mL (interquartile range 1938–5511 pg/mL). Participants in the highest tertile of baseline GDF‐15 were more likely to be male and have more co‐morbidities. After adjustment, an increase in GDF‐15 over 30 days was associated with higher risk of death or HHF [hazard ratio 1.35, 95% confidence interval (CI) 1.11–1.64]. In addition, higher baseline GDF‐15 (per 1000 pg/mL until 6000 pg/mL) and an increase in GDF‐15 over 30 days were associated with declining 6 min walk distance (odds ratio 1.26, 95% CI 1.02–1.55 and odds ratio 1.37, 95% CI 1.12–1.69, respectively). GDF‐15 levels remained stable among participants randomized to liraglutide. Conclusions An increase in GDF‐15 over 30 days among patients in HFrEF was independently associated with an increased risk of cardiovascular events and declining exercise capacity. These results support the value of longitudinal GDF‐15 trajectory in informing risk of heart failure disease progression.
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spelling doaj.art-385af4f80c514fc69c535399a22fde822022-12-21T22:55:23ZengWileyESC Heart Failure2055-58222021-08-01842608261610.1002/ehf2.13348Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failureAbhinav Sharma0Stephen Greene1Muthiah Vaduganathan2Marat Fudim3Andrew P. Ambrosy4Jie‐Lena Sun5Steven E. McNulty6Adrian F. Hernandez7Barry A. Borlaug8Eric J. Velazquez9Robert J. Mentz10Adam D. DeVore11Brooke Alhanti12Kenneth Margulies13G. Michael Felker14DREAM‐CV Lab, McGill University Health Centre McGill University Montreal Quebec CanadaDuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USABrigham and Women's Hospital Heart and Vascular Center Harvard Medical School Boston MA USADREAM‐CV Lab, McGill University Health Centre McGill University Montreal Quebec CanadaKaiser Permanente San Francisco Medical Center San Francisco CA USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USADepartment of Cardiovascular Medicine Mayo Clinic Rochester MN USACardiovascular Medicine, Department of Internal Medicine Yale University School of Medicine New Haven CT USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USAUniversity of Pennsylvania School of Medicine Philadelphia PA USADuke Clinical Research Institute Duke University 200 Morris Street Durham NC 27701 USAAbstract Aims Associations between growth differentiation factor‐15 (GDF‐15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the ‘Functional Impact of GLP‐1 for Heart Failure Treatment’ (FIGHT) study to address these knowledge gaps. Methods and results FIGHT was a randomized clinical trial testing the effect of liraglutide (vs. placebo) among 300 participants with HFrEF and a recent HHF. Multivariable regression models evaluated associations between baseline GDF‐15 and change in GDF‐15 (per 1000 pg/mL increase from baseline to 30 days) with clinical outcomes (at 180 days) and declines in exercise capacity (6 min walk distance ≥ 45 m). At baseline (n = 249), median GDF‐15 value was 3221 pg/mL (interquartile range 1938–5511 pg/mL). Participants in the highest tertile of baseline GDF‐15 were more likely to be male and have more co‐morbidities. After adjustment, an increase in GDF‐15 over 30 days was associated with higher risk of death or HHF [hazard ratio 1.35, 95% confidence interval (CI) 1.11–1.64]. In addition, higher baseline GDF‐15 (per 1000 pg/mL until 6000 pg/mL) and an increase in GDF‐15 over 30 days were associated with declining 6 min walk distance (odds ratio 1.26, 95% CI 1.02–1.55 and odds ratio 1.37, 95% CI 1.12–1.69, respectively). GDF‐15 levels remained stable among participants randomized to liraglutide. Conclusions An increase in GDF‐15 over 30 days among patients in HFrEF was independently associated with an increased risk of cardiovascular events and declining exercise capacity. These results support the value of longitudinal GDF‐15 trajectory in informing risk of heart failure disease progression.https://doi.org/10.1002/ehf2.13348GDF‐15Heart failureLiraglutideGLP‐1 receptor agonist
spellingShingle Abhinav Sharma
Stephen Greene
Muthiah Vaduganathan
Marat Fudim
Andrew P. Ambrosy
Jie‐Lena Sun
Steven E. McNulty
Adrian F. Hernandez
Barry A. Borlaug
Eric J. Velazquez
Robert J. Mentz
Adam D. DeVore
Brooke Alhanti
Kenneth Margulies
G. Michael Felker
Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
ESC Heart Failure
GDF‐15
Heart failure
Liraglutide
GLP‐1 receptor agonist
title Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
title_full Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
title_fullStr Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
title_full_unstemmed Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
title_short Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
title_sort growth differentiation factor 15 treatment with liraglutide and clinical outcomes among patients with heart failure
topic GDF‐15
Heart failure
Liraglutide
GLP‐1 receptor agonist
url https://doi.org/10.1002/ehf2.13348
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